The present invention relates generally to radiolabeled implantable devices and, more particularly, to radiolabeled stents for reducing restenosis, and methods and apparatuses for their production and use.
Vessel stenosis in humans and animals can occur, for example, by obstruction of the vessels (e.g., arteriosclerosis) or by external pressure (e.g., tumors) being applied on the vessels. After stenotic sites are treated (e.g., by balloon angioplasty) to clear or enlarge the obstructed or constricted vessels, stents are often placed within the vessel to prevent restenosis (the re-occlusion of vessels). Nevertheless, restenosis still occurs in a significant number of patients.
While the cause of restenosis is not clearly understood, it is believed that proliferation of smooth muscle cells in the treated vessels results in scar tissue formation, which can eventually lead to blood flow restriction or blockage in the vessels. Because local irradiation has been shown to reduce the growth of smooth muscle cells, one approach to prevent restenosis is to locally irradiate the stenotic site after stent deployment. Another approach, as disclosed in U.S. Pat. No. 5,059,166 to Fischell et al. (“the '166 patent”), is to implant a radioactive stent in the treated vessel to inhibit smooth muscle cell growth and thereby prevent restenosis.
As discussed in “Electrodeposition of Radioactive Rhenium onto Stents to Prevent Restenosis,” by Urs O. Häfeli et al., Biomaterials, Vol. 19, pgs. 925-933 (1998) (“Biomaterials”), radioactive stents currently need to be produced and activated in advance of implantation, and therefore cannot be tailored—by stent length and type or by radioactivity level—for individual lesion characteristics. Biomaterials suggests an approach whereby radioactive stents can be produced in 15 minutes, just prior to implantation. In Biomaterials, radioactive stents are produced by coating conventional stainless steel or tantalum stents with radioactive rhenium. The conventional stent is placed in a series of rinsing and electroplating solutions, one of which contains radioactive rhenium (186Re or 188Re or both). The plated stent contains radioactive rhenium in a 1.2 μm-thick cobalt layer, with an outer 2 μm-thick layer of gold. According to Biomaterials, the gold layer provides the radioactive stent with excellent chemical stability, good bending and biocompatibility properties, and improved visibility during fluoroscopy.
While Biomaterials appears to have made significant strides in the production of radioactive stents, a number of improvements relating to radioactive stents and their production and use in clinical environments are desirable. For example, recent studies (e.g., “Edge Restenosis after Implantation of High Activity P-32 Radioactive Beta-Emitting Stents,” Albiero et al., Circulation 2000, 101:2454-2457) indicate that restenosis can and does occur at the ends of radioactive stents implanted in treated vessels. A current theory attributes the cause of this “candy wrapper” restenosis to the radioactivity level of the radioactive stent. If the radiation dosage is too low or too short in duration, smooth muscle cell growth occurs and eventually the vessel wall at the ends of the stent constricts or closes. On the other hand, if the radiation dose is too high or too long in duration, the tissue behind the smooth muscle cells constricts in reaction to the radiation, thereby constricting or closing the vessel by external pressure. Thus, a need exists for a radioactive stent that delivers an optimal amount of radiation to a stenotic site to prevent restenosis.
In addition, a need exists for an electrochemical deposition technique whereby radioactive stents and other implantable devices are easily and safely produced with little or no intervention by hospital or technical personnel. For example, it is desirable to provide an electrochemical deposition technique that requires a limited number of electrolytic cells and/or solutions to produce a radioactive implantable device, such as a stent.
Furthermore, improved techniques for preparing implantable devices for radiolabeling, for optimizing the surface finish of radioactive implantable devices and for customizing and adjusting the radioactivity level of radioactive implantable devices are desirable.